Alzheimer's disease is a debilitating condition that wil increase in prevalence as the population continues to age. It is expected that the USA will see 16 million cases by 2050. There is a need for better molecular biomarkers and molecular imagers to detect this horrible disease at its earliest stages and assist with the development/monitoring of the efects of new drugs and therapeutic strategies. Molecular imaging with its high sensitivity and specificity offers the best chance to provide the necessary tools to diagnose, guide and monitor therapy of Alzheimer's and other dementia diseases. These imagers need to offer high sensitivity and high resolving power. Standard clinical nuclear medicine imagers used for positron imaging (PET) or single gamma (SPECT) are not optimized for imaging the brain at a high resolution of one to a few mm. PET is the preferred modality due to its intrinsically high resolution and high efficiency operation. Although there have been advances in specialized PET systems for brain imaging, they are not portable and limit the types of studies which can be performed due to the bulky size of the detector heads. Thus we propose a fully wearable Helmet-PET system using the new, very compact Silicon Photomultiplier technology. Our device will move with the person's head and allow the person to sit, stand, run in place (on a treadmill) and even make minor side movements, therefore it is sitting-, standing-, and limited movement- tolerant. In addition, this technology is MRI compatible and can be used as a PET insert for MRI/fMRI imaging. A wearable imager is constantly co-registered to the patient's head and thus movement artifacts are greatly minimized in order to achieve high spatial resolution scans. In addition, because of increased system efficiency with the detector modules placed close to the brain, lower injection doses are possible. This wil enable more imaging sessions for a patient without increasing the radiation dose in cases of following the progression/regression of disease, treatment monitoring, etc, in addition to lowering the cost per scan. Also, due to the Partial Volume Effect the sensitivity of the imager to detect features of 1-2mm will be increased by a substantial factor as the indirect result of the increased resolution. We will use arrays of SiPMs coupled to arrays of LYSO crystals with compact readout electronics to produce a multi-ring PET imager with a 26 cm inner diameter and initialy 5cm and ultimately 15cm in height. This compact ring will be sandwiched between inner and outer lightweight housing shells to produce a Helmet- PET brain scanner. The weight of the system will be supported by a properly designed mechanical system with a flexible suspension arm/cable. This support system will provide a path for the associated signal cables from the detector modules to the externally located (in a mobile cabinet) data acquisition system. The final goal is to achieve a practical robust performance approaching 1mm spatial resolution at 10 times the efficiency of standard PET scanners, with a viable system complexity and sustainable cost. PUBLIC HEALTH RELEVANCE: This research will help to diagnose and manage Alzheimer's disease while containing costs and lowering radiation dose to the patient. It will allow research studies which were not able to be performed in the past and assist in the development of new treatments in the search for a cure for Alzheimer's. It also may open the doors for research into other brain diseases such as Parkinson's disease.